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Program synthesis means that the computer automatically constructs code that conforms to the specified grammar and user’s given specifications.Programming by examples is a kind of paradigm in program synthesis that takes input and output examples as the specifications.It has high usability and low learning cost.In recent years,it has been successfully implemented in applications such as data wrangling and string transformation,and has great potential for development.There are two main pro-blems to be solved in programming by examples.One is the problem of efficient search in huge program space,and the other is the problem of ambiguity in solutions.To solve the first problem,a method for programming by examples needs to select the appropriate domain-specific language and formulate the search algorithm when specifying the searching strategy.The applied searching algorithm can be classified into a rule-based algorithm and an algorithm based on statistical model.To solve the second problem,a method for programming by examples needs to formulate a sorting strategy.The applied sorting strategy can be classified into a sorting method based on given examples and a sorting method based on user interaction.This paper sorts out related literature on programming by examples in recent years,summarizes the methods and key technical points to solve the above two problems,and finally gives suggestions for future research directions in the field of programming by examples.

Objective: To analyze the aberrant der(X) chromosome using conventional and molecular cytogenetic approaches in a fetus of second trimester and to discuss its clinical effect., Methods: Conventional cytogenetic procedures (GTG and CBG banding) were performed on cultured amniotic fluid cells. Three-color fluorescence in situ hybridization (FISH) consisting of X chromosome enumeration probes(CEPX), CEPY and Tel Xp/Yp was further performed to study the aberrant der(X) chromosome., Results: Der(X) was a rare X/Y translocation. The final karyotypes of the fetus was designated as: 46,X,der(X)t(X;Y)(p22.3;q11.2). ish der(X)t(X;Y)(p22.3;q11.2)(X/Ypter-, DXZ1+, DYZ1+)mat., Conclusion: The combination of FISH and conventional cytogenetic techniques is a powerful tool to determine derivative chromosome and to offer an accurate genetic counseling. Identification of Xp; Yq rearrangement can help estimate the risk of fetus abnormalities and give a more precise prognosis.

Objective: To analyze the numerical aberration rate of X, Y and chromosome 18 in sperms from an oligozoospermic male with mosaic trisomy 18 and to perform preimplantation genetic diagnosis (PGD) for the couple., Methods: G-banding and fluorescence in situ hybridization (FISH) were performed on metaphase chromosome. Sperm was analyzed in three-color FISH with a probe mixture containing CEP18, CEPY and Tel Xq/Yq. A healthy man with normal semen parameters was used as control., Results: Significant difference in the rates of disomy for chromosome 18 (0.63% vs. 0.16%) and the gonosomes (0.945% vs. 0.35%) and diploidy (0.87% vs. 0.31%) was found in the spermatozoa between the patient and the control. After four embryos were biopsied in one PGD cycle, two embryos with XY1818 and XX1818 were selected for implanting and clinical pregnancy was ongoing., Conclusion: Sperm-FISH allows further understanding of aneuploidy rate and accurate genetic counseling. FISHPGD was effective for patient with mosaic trisomy 18.

Objective: To perform genetic analysis of a complex chromosome rearrangement (CCR) 46,XY, t(3;11)(q27; q13), ins(11;3)(q13;p26p13) in an azoospermic man., Methods: Peripheral blood lymphocytes we re obtained for karyotyping, and metaphases were studied by multicolor fluorescence in situ hybridization procedure, Y chromosomal microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction., Results: The case was a complex chromosomal translocation between chromosomes 3 and 11 with four breakpoints, and accompanied with a band of chromosome 3 inserting into chromosome 11. No Y-chromosome microdeletions were identified at 6 STS sequences of the AZF loci., Conclusion: CCR can have a significant impact on male fertility. Molecular cytogenetic techniques may contribute to improving and personalizing reproductive counseling.

Objective: To analyze the sex chromosome meiotic segregation in inv(Y) patients by fluorescence in situ hybridization (FISH)., Methods: Conventional cytogenetic procedures (GTG and CBG banding) and FISH were performed on metaphase chromosome. Three-color FISH was performed on sperm samples using a probe mixture containing CEPX, Tel Xp/Yp and Tel Xq/Yq to investigate the sex chromosome segregation of five inv(Y) (p11.1q11.2) carriers. A healthy man with normal semen parameters was used as control., Results: There was no statistical difference in the abnormal sex chromosome number and recombination frequencies in each spermatozoon from the patient in comparison with that in the control., Conclusion: There was no apparent sex chromosome abnormality in the sperm of the inv(Y) (p11.1q11.2) carriers. Sperm-FISH allows further understanding of the sex chromosome segregation pattern and an accurate genetic counseling.

Objectives: To observe the genetic characteristics of chromosomes and the rates of implantation and pregnancy in couples of translocation carriers who undergo preimplantation genetic diagnosis (PGD) and to evaluate the significance of PGD in the treatment of translocation carriers., Methods: Fluorescence in situ hybridization (FISH) was performed to analyze the embryos of 12 carriers of reciprocal translocation and 22 carriers of Robertsonian translocation. The results of diagnosis and the implantation and pregnancy rates were analyzed., Results: A total of 253 embryos from 36 couples were retrieved and FISH was applied for the examination. The characteristics of chromosomes were diagnosed in 225 embryos and the rate of successful PGD was 88.9%. Fifty-eight embryos were found to have normal chromosome or balanced translocation and were transferred into the uterus. The rate of implantation was 36% (5/14) and 14% (6/44) and the rate of pregnancy was 4/9 and 26% (5/19) for carriers of Robertsonian translocation and reciprocal translocation, respectively., Conclusions: The FISH-based PGD is effective in the diagnosis of Robertsonian translocation and reciprocal translocation of embryos. It provides the possibility of a high rate of implantation and pregnancy, and avoids recurrent abortion and unwilling termination of pregnancy.

Objective: To investigate aquaporin 9 (AQP9) mRNA and protein expression in antrum follicle and luteinizing granulosa cells of polycystic ovarian syndrome (PCOS) ovary, and its relation to follicular fluid steroids hormone levels during IVF cycles., Methods: AQP9 mRNA expression on luteinizing granulosa cells in IVF cycles was detected by RT-PCR. AQP9 protein expression in antrum follicles of PCOS ovary and luteinizing granulosa cells was measured by immunohistochemistry. The concentrations of estradiol (E2), progesterone (P) and testerone (T) in follicular fluid were measured by radioimmunoassay (RIA)., Result: The expression of AQP9 mRNA in luteinizing granulosa cells during IVF cycles was positive by RT-PCR. No significant differences in AQP9 mRNA levels in granulosa cells between PCOS and control group were found during IVF cycles. The expression level of AQP9 mRNA in large follicles was higher than that in small follicles, but not significantly. The immunoreactivity for AQP9 was localized in membrane and cytoplast of granulosa cells in antrum follicles from PCOS ovary and luteinizing granulosa cells during IVF cycles. Multiple regression analysis showed that AQP9 mRNA levels on granulosa cells were not correlated with E2, P and T levels in follicular fluid during IVF cycles., Conclusion: AQP9 may play an important role in the follicle development and antrum formation through water transport and AQP9 may be involved in the mechanism of follicle development in PCOS.

Objective: To investigate the influence of different cycles, ovarian follicle size and IVM culture media on the number of retrieved immature oocytes, maturation rate, fertilization rate, embryo quality and implantation rate, pregnancy rate, delivery rate, survival and development of frozen-thawed embryos from IVM., Methods: The oocytes were obtained by follicular aspiration from 19 women undergoing oocyte retrieval for in vitro maturation due to the possible risk of ovarian hyperstimulation in IVF-ET program. One patient was in natural cycle, four patients were in ovulation induction cycles with gonadotropine and fourteen patients is controlled ovarian stimulated cycles. All the oocytes retrieved from follicles with 10.0 - 13.5 mm in maximumdiameter were allowed to culture in medium M-199 (TCM 199) or HTF supplemented with other substance., Result: When there were nonuniform diameters of follicles and the diameter of largest oocyte exceeded 12 mm, the retrieval rate of oocytes, fertilization rate, and the number of high-quality embryos decreased. The high-quality embryos formation rate was higher for the oocytes cultured in TCM 199 medium than in HTF medium (P<0.01). After being frozen-thawed, the IVM embryos could achieve the same outcome when compared with the conventional IVF treatment. In addition, the offspring were healthy., Conclusion: When the nonuniform diameters of follicles and the diameter of largest oocyte exceeds 12 mm,the retrieval rate of oocytes, fertilization rate, and the number of high-quality embryos decreased. TCM199-based medium is better to improve the developmental potential and implantation rate of embryos derived from in vitro matured oocytes. After being frozen-thawed, the IVM embryos could achieve the same outcome when compared with the conventional IVF treatment. In addition, the offspring are healthy.

To investigate the expression patterns of histone acetyltransferase (GCN5) and histone deacetylase 1 (HDAC1) in preimplantation mouse embryos and the effects of in-vitro cultures on their expressions, immunocytochemistry was used to detect the expressions of GCN5 and HDAC1 in mouse embryos at the stages of two-cell, four-cell, eight-cell, morula and blastocyst in both in-vivo and invitro groups. In in-vivo group, the obvious expressions of GCN5 were observed in the cytoplasm of all kinds of mouse embryos but blastocysts. Meanwhile, HDAC1 was highly expressed in the nuclei of four and eight-cell embryos and morula but mainly seen in the cytoplasm of two-cell embryos. In blastocysts, the HDAC1 fluorescence was limited to the nuclei of trophoblast cells. In in-vitro group, there were no obvious GCN5 expressions in all kinds of embryos and the expression of HDAC1 was significantly reduced although its expression pattern was similar to that of in-vivo group. Those results showed that in -vitro culture environments could inhibit GCN5 expression and decrease the expression of HDAC1 in mouse preimplantation embryos, which might affect the correct embryonic gene expression.

Objective: To investigate protein and mRNA expression of aquaporin-1 (AQP1) in epithelial ovarian tumors and its clinic significance., Methods: The protein and mRNA expressions of AQP1 were measured by immunohistochemical technique, western blot and RT-PCR in 65 cases of epithelial ovarian tumors and 13 cases of normal ovary tissue., Results: AQP1 located in microvascular and small vessel epithelial cells. The protein and mRNA expressions of AQP1 in ovarian cancer (0.39 +/- 0.12, 0.93 +/- 0.51, respectively) and ovarian borderline tumors (0.43 +/- 0.21, 0.95 +/- 0.34, respectively) were significantly higher than that of ovarian benign tumors (0.27 +/- 0.13, 0.51 +/- 0.41, respectively; P < 0.05) and normal ovary tissue (0.24 +/- 0.13, 0.34 +/- 0.29, respectively; P < 0.05). Of all ovarian cancers, expression of AQP1 in cases with ascites more than 1000 ml (0.46 +/- 0.13, 1.25 +/- 0.57, respectively) was higher than that of ascites less than 1 approximately 499 ml (0.35 +/- 0.11, 0.75 +/- 0.45, respectively; P < 0.05)., Conclusion: Over-expression of AQP1 plays an important role in development of epithelial ovarian tumors, and may be related with formation of ascites of ovarian carcinoma.

Objective: To investigate the role of interleukin-17 (IL-17) in the pathogenesis of endometriosis., Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of IL-17 in peritoneal fluid of 36 patients with different stage endometriosis and 26 patients without endometriosis., Results: The concentrations of IL-17 in peritoneal fluid of the patients with and without endometriosis were (5.7 +/- 1.9) ng/L and (5.3 +/- 1.4) ng/L, respectively, without significant difference between the two groups (P > 0.05). According to staging criteria of r-AFS, the concentrations of peritoneal IL-17 in the patients with stage I-II endometriosis (6.4 +/- 1.7) ng/L were significantly higher than those in the patients with stage III-IV endometriosis (5.1 +/- 1.8) ng/L and in the patients without endometriosis (P < 0.05). There was no difference with regard to peritoneal IL-17 concentrations between proliferative and secretory phases in the patients with or without endometriosis (P > 0.05). The levels of peritoneal IL-17 were significantly higher in the endometriosis patients with infertility (6.4 +/- 1.8) ng/L than in the endometriosis patients without infertility (5.1 +/- 1.8) ng/L (P < 0.05)., Conclusion: IL-17 may play an important role in the pathogenesis of early endometriosis and pathophysiology of endometriosis-associated infertility.

Objective: To investigate insulin receptor (INSR) genotype exon 17 frequencies in women with polycystic ovary syndrome (PCOS) and to elucidate its role in the pathogenesis of PCOS., Methods: The study involved 33 women with PCOS and 28 healthy control women who were genotyped for polymorphism of INSR gene exon 17 by single strand conformation polymorphism (SSCP) analysis. Body mass index (BMI), insulin sensitive index (ISI), the expression of INSR beta subunit, and serum concentration of luteinizing hormone (LH), total testosterone between the genotypes were compared., Results: (1) The T-to-C mutation was observed in the INSR gene exon 17 (1008 bp). The frequency of the C/C genotype was significantly higher in patients (39%) than in the controls (11%) (P < 0.05). There was no significant difference in the distribution of genotypes between obese PCOS and non-obese PCOS, and between PCOS with insulin resistance (IR) and PCOS without IR. (2) In comparison of mutation genotype groups with wild genotype (T/T), ISI was significantly decreased (C/C genotype, P < 0.01; C/T genotype, P < 0.05), and no significant difference was observed in the other indices., Conclusions: There is polymorphism in INSR gene exon 17 in patients with PCOS. This variant leads to increased risk of IR in women with PCOS. It does not influence the expression of INSR beta subunit.

Objective: To explore the relationship between the patients' high follicle-stimulating hormone (FSH) azoospermia and microdeletions in Y chromosome., Methods: Eleven sequence tagged sites (STSs) in Yq were detected by PCR in 16 male patients' high FSH azoospermia., Results: Microdeletions were observed in 6 of 16 male patients and the deletion rate was 37.5%(6/16). Five types of microdeletions were detected: AZFc(SY152), AZFc (SY152+SY254)+AZFd (SY153), AZFc (SY152+SY254+SY255)+AZFd (SY153), AZFc (SY152+SY158+SY255)+AZFd (SY153),and AZFb (SY130)+AZFc (SY158+SY254+SY255)+AZFd (SY153) respectively., Conclusion: Microdeletion of Y chromosome was one of the important reasons of the patients' high FSH azoospermia. Before the application of assisted-reproductive technology (ART) to the patients, it is necessary to detect the microdeletions, especially AZFc and AZFd.

Objective: To perform preimplantation genetic diagnosis (PGD) of chromosome abnormality using fluorescence in-situ hybridization (FISH)., Methods: Ten couples were presented for preimplantation genetic diagnosis. They had a total of 10 oocyte pick-up cycles. The collected oocytes were inseminated by intracytoplasmic sperm injection. PGD was carried out using cleavage-stage (day 3) embryo biopsy, fluorescence in-situ hybridization, and day 4 embryo transfer., Results: Ten oocyte pick-up cycles yielded 158 oocytes. Among the 94 embryos obtained, 54 embryos were biopsied and FISH analyses were performed for 51 blastomeres. Twenty-four embryos were transferred on the fourth day. There were 4 clinical pregnancies: 3 infants have been born, and 1 couple had ectopic pregnancy., Conclusion: PGD is a valuable method to prevent the high risk of spontaneous miscarriages and conceiving chromosomally unbalanced offspring.

OBJECTIVE: To establish a technology of preimplantation genetic diagnosis. METHODS: Intracytoplasm sperm injection and blastomere biopsy were performed on two women at the advanced age with the fallopian tube obstruction. Normal embryos were selected for embryo transfer after fluorescence in-situ hybridziation in biopsied blastomere. RESULTS: The levels of serum HCG were increased 20 days after embryo transfer and ultrasonography in 16 gestation weeks showed the fetal growth and structure are normal. CONCLUSION: Two successful clinical pregnancies achieved after preimplantation genetic diagnosis.